Potential Mechanisms of Er Chen Decoction against Polycystic Ovary Syndrome Based on Network Pharmacology Strategy

Abstract

Background: Er Chen decoction (ECD), a time-honored herbal mixture, has been broadly used in gynecological diseases, including polycystic ovary syndrome (PCOS). PCOS is a common reproductive disorder characterized by endocrine and metabolic dysfunction that has an increasing prevalence rate. However, the bioactive components in ECD and their underlying mechanisms for treating PCOS remain unknown. This study aimed to predict potential mechanisms of ECD in treating PCOS, through network pharmacology strategy. Methods: The bioactive compounds of ECD and therapeutic targets were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and potential targets of PCOS were acquired from Online Mendelian Inheritance in Man (OMIM) and Genecards database. Afterward, the ECD-Ingredient-PCOS-target regulation network, topology network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were performed to predict the core targets and pathways of ECD against PCOS. Results: A total of 156 potential targets were matched with 116 related bioactive ingredients and regulation network revealed their interactions. Network topology analysis showed the top 10 core proteins in ECD against PCOS to be TP53 (Tumor Protein P53), CUL3 (Cullin 3), YWHAZ (Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta), HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1), MCM2 (Minichromosome Maintenance Complex Component 2), NPM1 (Nucleophosmin 1), VCP (Valosin Containing Protein), CUL1 (Cullin 1), NTRK1 (Neurotrophic Receptor Tyrosine Kinase 1), COPS5 (COP9 Signalosome Subunit 5). GO analyses identified 1986 items of biological progress (BP), 58 items of cellular components (CC) and 186 items of molecular function (MF). KEGG functional enrichment analysis identified 167 signaling pathways, such as IL-17 (Interleukin-17) signaling pathway, TNF (Tumor Necrosis Factor) signaling pathway. ECD-gene-pathway network revealed that target genes MAPK1, CASP3, BAX, BCL2 and others were involved in numerous signaling pathways and every pathway was abundantly enriched by multiple genes. Conclusions: This preliminary study explored the potential mechanisms of ECD in treating PCOS, suggesting that the bioactive components of ECD, such as quercetin, kaempferol, naringenin and β-sitosterol, might treat PCOS by regulating IL-17, TNF and other signaling pathways as well as MAPK1, CASP3, BAX, BCL2 and other target genes. These results supplied novel comprehension of pharmacological mechanisms of ECD in treating PCOS in multiple dimensions.